VN June 2023

Vetnuus | June 2023 10 Dr Tom Stout Department of Clinical Sciences, Utrecht University, The Netherlands T.A.E.Stout@uu.nl Abstract Over the last 30 years, improvements in veterinary management have resulted in higher per-cycle pregnancy rates in commercial horse breeding programs. However, the incidence of early pregnancy loss has not diminished, and ~ 10% of pregnancies detected on day 15 fail to survive beyond day 42. To develop methods to combat pregnancy loss, it is first necessary to understand why these pregnancies fail. In this respect, a sizeable proportion probably results from intrinsic embryonic abnormalities that cannot be remedied; another significant subset is, however, likely to result from an‘inadequately receptive’ uterus or failure of the uterus to physiologically adapt to the developing conceptus’ changing needs, as a result of inadequate embryo-maternal communication. Communication between embryo and dam starts during the oviductal period, as evidenced by the selective transport of viable embryos into the uterus on day six after ovulation, whereas unfertilized oocytes remain in the oviduct. Conversely, retarded development exhibited by embryos produced in vitro demonstrates the importance of the oviductal environment to the early embryo. Once in the uterus, the embryo must steer the endometrium for implantation. This communication includes‘maternal recognition of pregnancy’ signalling to extend the lifespan of the primary corpus luteum and ensure continued secretion of progesterone. Although the identity of the embryotic pregnancy recognition signal remains unknown, our understanding of how endometrial function is altered to avert prostaglandin F2a release and become receptive to implantation has improved. Introduction Sincethe1970s,technologicalandpharmacologicaldevelopments, allied to a better understanding of factors that compromise fertility, have led to a marked rise in the per-cycle pregnancy rate in intensively managed horses. During the same period, assisted reproductive technologies (e.g.embryo and oocyte transfer) and more recent ovum pick-up and intracytoplasmic sperm injection (ICSI) for in vitro embryo production have been adopted commercially either to circumvent certain forms of subfertility or to aid genetic improvement. Despite the successful introduction of these techniques to overcomesubfertilityandthegeneralimprovementinreproductive efficiency, there has been little progress in combating one of the major sources of economic loss within horse breeding, namely early pregnancy loss. After the initial detection of pregnancy at around day 15 post-ovulation, approximately 5 - 15 % of all pregnancies will fail to reach term in young, healthy mares, often without any obvious explanation for why the pregnancy was lost. Pregnancy losses are even more common in older (>18 years) mares or following the transfer of invitro produced embryos, where >15% of day 15 pregnancies are reported to fail. Interestingly, more than half of all pregnancy losses occur in the first six weeks of pregnancy. This strong bias to early loss is presumably in large part because conceptuses with serious intrinsic defects, such as gross abnormalities of chromosome number (aneuploidy), are most likely to fail during early development. Moreover, the equine conceptus undergoes a remarkable transformation during the first seven weeks of life, from a microscopic ball of undifferentiated cells that imbibes nutrients from the surrounding oviductal fluids to a fetus with recognizable body parts and precursor of all the major organs required for extrauterine life, that is provided with nutrients by a dedicated placenta. Embryo-maternal communication during the establishment of equine pregnancy